OBJECTIVES: We analyzed qualitative and quantitative data for 98 HIV-negative, low-risk women in Malawi, Zimbabwe, India, and Thailand who participated in a safety and acceptability study of BufferGel, a vaginal microbicide to determine the across-country acceptability of vaginal microbicides among women and their partners. METHODS: Quantitative survey data were collected at 7 and 14 days after use among enrolled women, and exit interviews were conducted with women and their partners in separate focus group discussions. RESULTS: Acceptability was high in all sites (73% of women approved of the microbicide). Women in Africa, where HIV infection rates are highest, were virtually unanimous in their desire for such a product, suggesting that an individual's perception of being at risk for HIV will outweigh concerns about side effects, problems applying a product, or other factors, when products are shown to be efficacious. But men and women reported that use, which was kept secret from an intimate partner, would be difficult and might "break the trust" of a relationship. CONCLUSIONS: Acceptability research across diverse settings through all stages of microbicide research, development, and post-licensure dissemination can help maximize acceptability and use.